Project Summary Hearing impairment is one of the most common sensory abnormalities in humans, affecting nearly 30 million people in the United States. Hearing impairments are caused by several pathogenic processes including structural and genetic defects, infections, environmental exposures and trauma. Pathogenic effects on the peripheral auditory system (ear, cochlea, and auditory nerve) are well-described, and several animal models have been created to study them. However, a dearth of animal models to study normal and disrupted embryogenesis of the central auditory system has led to an incomplete understanding of developmental processes that control central auditory neuron specification, differentiation, axonal targeting, and trophic interactions. This, in turn, has limited our understanding of pathophysiological mechanisms and their consequences on the central auditory system. The overall goal of this proposal is to understand how disruptions of brain morphogenesis affect central auditory system development, connectivity and function. We have developed new mouse models that will, for the first time, allow us to study these processes as they relate to inferior colliculus (IC) and superior olivary complex (SOC) neurons. We expect that insights gained from these models will inform us as to how disruptions of auditory neuron development can contribute to human hearing disorders.